Coelho David R A, Yang Chen, Suriaga Armiel, Manasa Justen, Bain Paul A, Vieira Willians Fernando, Papatheodorou Stefania, Salvi Joshua D
Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Countway Library, Harvard Medical School, Boston, Massachusetts.
JAMA Netw Open. 2025 Jan 2;8(1):e2452963. doi: 10.1001/jamanetworkopen.2024.52963.
Obsessive-compulsive and related disorders (OCRDs) encompass various neuropsychiatric conditions that cause significant distress and impair daily functioning. Although standard treatments are often effective, approximately 60% of patients may not respond adequately, underscoring the need for novel therapeutic approaches.
To evaluate improvement in OCRD symptoms associated with glutamatergic medications as monotherapy or as augmentation to selective serotonin reuptake inhibitors, with a focus on double-blind, placebo-controlled randomized clinical trials (RCTs).
Electronic searches were conducted in PubMed, Embase, PsycINFO, Web of Science, and Cochrane Central Register of Controlled Trials on October 16, 2024, without date limits.
Two investigators independently screened records to identify double-blind RCTs comparing glutamatergic medications with placebo for patients with OCRDs regardless of age, sex, gender, or refractoriness. Abstracts, study protocols, non-English studies, and trials involving augmentation to psychotherapy were excluded.
Data were extracted and synthesized using random-effects meta-analyses. Subgroup analysis was conducted based on type of OCRD, population, refractoriness of OCRD, augmentation strategy, risk of bias, and type of glutamatergic medication. Sensitivity analysis was performed using a leave-one-out approach.
Improvement in OCRD symptoms was measured by standardized mean difference (Cohen d). Improvement in obsessive-compulsive disorder (OCD) symptoms was measured by mean difference (reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] scores).
A total of 27 RCTs (1369 participants; mean [SD] age, 31.5 [7.8] years; 65.6% female) were included. Glutamatergic medications showed a large effect size in improving OCRD symptoms (Cohen d = -0.80 [95% CI, -1.13 to -0.47]; low certainty of evidence). In the 23 OCD-specific RCTs, glutamatergic medications demonstrated a significant mean reduction in Y-BOCS scores (mean difference, -4.17 [95% CI, -5.82 to -2.52]; moderate certainty of evidence).
These findings indicate that glutamatergic medications may be effective in treating OCRDs, particularly OCD. However, high heterogeneity and potential publication bias necessitate cautious interpretation. Further research with larger sample sizes is needed to explore dose-dependent effects, additional OCRD subtypes, and other promising glutamatergic medications.
强迫症及相关障碍（OCRD）涵盖多种神经精神疾病，这些疾病会导致严重困扰并损害日常功能。尽管标准治疗通常有效，但约60%的患者可能反应不佳，这凸显了对新型治疗方法的需求。
评估谷氨酸能药物作为单一疗法或作为选择性5-羟色胺再摄取抑制剂的增效剂治疗OCRD症状的改善情况，重点关注双盲、安慰剂对照的随机临床试验（RCT）。
于2024年10月16日在PubMed、Embase、PsycINFO、Web of Science和Cochrane对照试验中央注册库进行电子检索，无日期限制。
两名研究者独立筛选记录，以识别比较谷氨酸能药物与安慰剂治疗OCRD患者的双盲RCT，无论患者年龄、性别、性取向或难治性如何。排除摘要、研究方案、非英文研究以及涉及心理治疗增效的试验。
使用随机效应荟萃分析提取并合成数据。根据OCRD类型、人群、OCRD难治性、增效策略、偏倚风险和谷氨酸能药物类型进行亚组分析。使用逐一排除法进行敏感性分析。
通过标准化均数差（Cohen d）衡量OCRD症状的改善情况。通过均数差（耶鲁-布朗强迫量表[Y-BOCS]评分降低）衡量强迫症（OCD）症状的改善情况。
共纳入27项RCT（1369名参与者；平均[标准差]年龄为31.5[7.8]岁；65.6%为女性）。谷氨酸能药物在改善OCRD症状方面显示出较大的效应量（Cohen d = -0.80[95%置信区间，-1.13至-0.47]；证据确定性低）。在23项特定于OCD的RCT中，谷氨酸能药物显示Y-BOCS评分显著平均降低（均数差，-4.17[95%置信区间，-5.82至-2.52]；证据确定性中等）。
这些发现表明谷氨酸能药物可能对治疗OCRD有效，尤其是OCD。然而，高度异质性和潜在发表偏倚需要谨慎解读。需要进行更大样本量的进一步研究，以探索剂量依赖性效应、其他OCRD亚型以及其他有前景的谷氨酸能药物。
